Designer Receptors for Nucleotide‐Resolution Analysis of Genomic 5‐Methylcytosine by Cellular Imaging

Abstract: We report programmable receptors for the imaging‐based analysis of 5‐methylcytosine (5mC) in user‐defined DNA sequences of single cells. Using fluorescent transcription‐activator‐like effectors (TALEs) that can recognize sequences of canonical and epigenetic nucleobases through selective repeats, we imaged cellular SATIII DNA, the origin of nuclear stress bodies (nSB). We achieve high nucleobase selectivity of natural repeats in imaging and demonstrate universal nucleobase binding by an engineered repeat. We use TALE pairs differing in only one such repeat in co‐stains to detect 5mC in SATIII sequences with nucleotide resolution independently of differences in target accessibility. Further, we directly correlate the presence of heat shock factor 1 with 5mC at its recognition sequence, revealing a potential function of 5mC in its recruitment as initial step of nSB formation. This opens a new avenue for studying 5mC functions in chromatin regulation in situ with nucleotide, locus, and cell resolution.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Designer Receptors for Nucleotide‐Resolution Analysis of Genomic 5‐Methylcytosine by Cellular Imaging ; volume:132 ; number:23 ; year:2020 ; pages:9012-9016 ; extent:5
Angewandte Chemie ; 132, Heft 23 (2020), 9012-9016 (gesamt 5)

Creator
Muñoz‐López, Álvaro
Buchmuller, Benjamin
Wolffgramm, Jan
Jung, Anne
Hussong, Michelle
Kanne, Julian
Schweiger, Michal R.
Summerer, Daniel

DOI
10.1002/ange.202001935
URN
urn:nbn:de:101:1-2022053106580445816723
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
15.08.2025, 7:35 AM CEST

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Associated

  • Muñoz‐López, Álvaro
  • Buchmuller, Benjamin
  • Wolffgramm, Jan
  • Jung, Anne
  • Hussong, Michelle
  • Kanne, Julian
  • Schweiger, Michal R.
  • Summerer, Daniel

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